A Surface Phase Model of the Alveolar Lining: Ultrastructural Analysis and in vivo Applications

Research output: ThesisDoctoral Thesis (compilation)

Abstract

In this thesis the relation between lung surfactant structure and functional properties have been studied.

Experimental results show that the alveolar surface is formed by a coherent surface phase with a structure equal to tubular myelin. The properties of this phase may explain certain unresolved issues in lung physiology, e.g., mechanical stability of surfactant during the breathing cycle, the question of free water in the alveolus, and uptake kinetics of pulmonary administered drugs. A surface phase has important consequences in general for the barrier function of the lung, and for host defense.

This surface phase is modeled with a biomathematical approach and is proposed to have a bilayer structure of a minimal surface type, the so-called CLP surface. This structure corresponds to a surfactant bilayer without self-intersections. The functional and structural properties of the CLP surface may explain e.g., the ultra low surface energy of surfactant in vivo, and rapid deformability of the surface phase during breathing.

The role of cholesterol in lung surfactant was studied by X-ray diffraction. It was shown that the presence of cholesterol lowers the crystallization temperature of the surfactant significantly.

During work with a pharmacy-grade lung surfactant, a novel dynamic swelling behavior was observed. During swelling in electrolyte containing water solutions, a dramatic increase of the air-water surface area was seen. In vivo evaluation of this process in an ARDS model was performed, showing significantly higher arterial oxygen levels in rats treated with surfactant in dynamic swelling compared to normal surfactant therapy.

Details

Authors
  • Marcus Larsson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Radiology, Nuclear Medicine and Medical Imaging

Keywords

  • X-ray diffraction, cryo-TEM, dynamic swelling, ARDS, surface phase, surfactant replacement therapy, cholesterol, minimal surface, pulmonary surfactant, alveolar surface, Physiology, Fysiologi
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2002 Dec 6
Publisher
  • Marcus Larsson, N. Vallg. 4, 223 62 Lund, Sweden,
Print ISBNs91-628-5448-8
Publication statusPublished - 2002
Publication categoryResearch

Bibliographic note

Defence details Date: 2002-12-06 Time: 09:15 Place: Föreläsningssalen, Ingång 73, Plan 1 UMAS, Malmö External reviewer(s) Name: Gil, Jesus Perez Title: Professor Affiliation: Dept. Bioquimica, Fac. Biologia, Universidad Complutense de Madrid 28040 Madrid, Spain --- Article: I. The alveolar surface structure: Transformation from a liposome-like dispersion into a tetragonal CLP bilayer phase.M. Larsson, K. Larsson, S. Andersson, J. Kakhar, T. Nylander, B. Ninham and P. WollmerJ Dispersion Sci Techn 20 (1999) 1 – 12. Article: II. The alveolar surface is lined by a coherent liquid-crystalline phase.M. Larsson, K. Larsson and P. WollmerProgr Colloid Polym Sci 120 (2002) 28 – 34 Article: III. Enhanced efficacy of porcine lung surfactant extract by utilization of its aqueous swelling dynamics.M. Larsson, J.J. Haitsma, B. Lachmann, K. Larsson, T. Nylander and P, Wollmer.Clin Physiol & Func Im 22 (2002) 39 – 48. Article: IV. The bilayer melting transition in lung surfactant bilayers: role of cholesterol.M. Larsson, K. Larsson, T. Nylander and P. WollmerEur Biophys J in press. Article: V. Human SP-A and a pharmacy-grade porcine lung surfactant extract can be reconstituted into tubular myelin – A comparative structural study of alveolar surfactants using cryo-transmission electron microscopy.M. Larsson, P. Wollmer, J. F. van Iwarden, J. J. Haitsma and B. Lachmann.Submitted. The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Clinical Physiology (013242300), Paediatrics (Lund) (013002000)